Effects of vibegron, a novel β3-adrenoceptor agonist, and its combination with imidafenacin or silodosin in a rat with partial bladder outlet obstruction.
Effects of vibegron, a novel β3-adrenoceptor agonist, and its combination with imidafenacin or silodosin in a rat with partial bladder outlet obstruction.
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Vibegron（一种新型 β3-肾上腺素受体激动剂）及其与咪达那新或西洛多辛联合用药对部分膀胱出口梗阻大鼠的影响。
DOI：
10.1016/j.ejphar.2020.173096
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发表时间：
2020
影响因子：
5
通讯作者：
T. Yamazaki
中科院分区：
文献类型：
--
作者：
I. Maruyama;Shota Yamamoto;Kumi Tsuchioka;T. Yamazaki
紧迫症被认为是膀胱过度活动(OAB)的核心症状，可能与逼尿肌过度活动(DO)相对应。男性OAB的原因之一是与良性前列腺增生症(BPH)相关的膀胱出口梗阻(BOO)。Vibegron是一种新型的选择性β3-肾上腺素能受体激动剂，最近被批准用于治疗OAB。然而，在合并BPH(BPH/OAB)的OAB患者中，Vibegron对存储功能，特别是DO和排尿功能的影响还没有得到充分的研究。在这项研究中，我们使用部分BOO的大鼠模型作为BPH/OAB的模型，评估了单次给药Vibegron对存储功能(特别是非排尿收缩[NVC]作为DO的替代标记)和排尿功能的影响。此外，还评价了Vibegron与咪达那新(一种抗心肌梗死药)或西来多辛(一种α1A-肾上腺素受体阻滞剂)联合应用的有效性。BOO建立后6周，膀胱测压显示NVC的频率和波幅均增加。Vibegron可抑制NVC频率，但不影响排尿功能(排尿压力、残余尿量和排尿效率)。咪达非那西林和西来多辛对NVC的频率也有抑制作用，但Vibegron的抑制作用强于咪达他克星和西来多辛。在不恶化排尿功能的情况下，Vibegron与咪达非他克星或西来多辛联合应用可额外抑制NVC的频率。这些结果表明，Vibegron作为单一药物可以有效地改善良性前列腺增生症/卵巢癌患者的储存症状，并与抗肌钙药物或α1肾上腺素受体阻滞剂联合使用。
Urgency is regarded as a core symptom of overactive bladder (OAB) and may correspond to detrusor overactivity (DO). One of the causes of OAB in men is bladder outlet obstruction (BOO) associated with benign prostatic hyperplasia (BPH). Vibegron is a novel selective β3-adrenoceptor agonist recently approved for the treatment of OAB. However, in OAB patients with BPH (BPH/OAB), the effects of vibegron on storage functions, especially DO and voiding functions have not been fully investigated. In this study, we evaluated the effects of a single administration of vibegron on storage function (particularly focusing on non-voiding contractions [NVC] considered a surrogate marker for DO) and voiding functions, using a rat model of partial BOO as a model for BPH/OAB. Furthermore, the utility of vibegron in combination with imidafenacin (an antimuscarinic) or silodosin (an α1A-adrenoceptor blocker) was evaluated. Six weeks after establishment of BOO, the frequency and amplitude of NVC, evaluated by cystometrography, increased. Vibegron inhibited the frequency of NVC without affecting voiding function (micturition pressure, residual volume, and voiding efficiency). Imidafenacin and silodosin also inhibited the frequency of NVC; however, the inhibitory effects of vibegron were stronger than those of imidafenacin or silodosin. The combination of vibegron with imidafenacin or silodosin additively inhibited the frequency of NVC without worsening the voiding function. These results suggest the possibility that vibegron is effective as a single agent for the amelioration of storage symptoms in BPH/OAB patients and is useful in combination with either antimuscarinics or α1-adrenoceptor blockers.
老年人逼尿肌功能的管理：衰老过程中乙酰胆碱和三磷酸腺苷释放的变化
影响因子：
2.1
作者：
Masaki Yoshida;et al.
通讯作者：
et al.
DOI：
10.1248/yakushi.126.237
发表时间：
2006-03-01
影响因子：
0.3
作者：
Matsubara, Y;Kanazawa, T;Midgley, I
通讯作者：
Midgley, I